Epigenetic regulation of steroidogenic enzymes expressed in peripheral blood mononuclear cells from healthy individuals and from patients with chronic lymphocytic leukemia

Author(s):  
Luisa Gaydou ◽  
Ma Florencia Rossetti ◽  
Ma Virginia Tschopp ◽  
Cora Stoker ◽  
Verónica L. Bosquiazzo ◽  
...  
2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Niloofar Ghanizade ◽  
Maral Hemati ◽  
Habib Jaafarinejad ◽  
Mehrnoosh Pashaei ◽  
Parviz Kokhaei

Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.


Blood ◽  
2012 ◽  
Vol 119 (7) ◽  
pp. e35-e44 ◽  
Author(s):  
Kwan-Ki Hwang ◽  
Xi Chen ◽  
Daniel M. Kozink ◽  
Marietta Gustilo ◽  
Dawn J. Marshall ◽  
...  

Abstract B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the clonal expansion of CD5-expressing B lymphocytes that produce mAbs often reactive with microbial or autoantigens. Long-term culture of B-CLL clones would permit the collection and characterization of B-CLL mAbs to study antigen specificity and of B-CLL DNA to investigate molecular mechanisms promoting the disease. However, the derivation of long-term cell lines (eg, by EBV), has not been efficient. We have improved the efficiency of EBV B-CLL transformation of CpG oligonucleotide-stimulated cells by incubating patient peripheral blood mononuclear cells in the presence of an irradiated mouse macrophage cell line, J774A.1. Using this approach, peripheral blood mononuclear cells isolated from 13 of 21 B-CLL patients were transformed as documented by IGHV-D-J sequencing. Four clones grew and retained CD5 expression in culture for 2 to 4 months. However, despite documentation of EBV infection by expression of EBNA2 and LMP1, B-CLL cells died after removal of macrophage feeder cells. Nevertheless, using electrofusion technology, we generated 6 stable hetero-hybridoma cell lines from EBV-transformed B-CLL cells, and these hetero-hybridomas produced immunoglobulin. Thus, we have established enhanced methods of B-CLL culture that will enable broader interrogation of B-CLL cells at the genetic and protein levels.


2010 ◽  
Vol 29 (6) ◽  
pp. 1156-1163 ◽  
Author(s):  
Lucia Pajuelo ◽  
Eva Calviño ◽  
Jose Carlos Diez ◽  
Maria del Carmen Boyano-Adánez ◽  
Juana Gil ◽  
...  

1993 ◽  
Vol 177 (4) ◽  
pp. 955-964 ◽  
Author(s):  
J Frishman ◽  
B Long ◽  
W Knospe ◽  
S Gregory ◽  
J Plate

Regulation of expression of interleukin 7 (IL-7) mRNA is aberrant in the leukemic subset of cells of chronic lymphocytic leukemia (CLL) patients. The entire coding sequence for IL-7 as well as an alternatively spliced IL-7 mRNA are transcribed in these leukemic cells. No IL-7 mRNA expression is detected in fresh peripheral blood mononuclear cells from normal individuals. Furthermore, the "normal" nonleukemic subsets of cells isolated from the same CLL patients also do not express IL-7 mRNA. The only subset of cells in which IL-7 mRNA is detected is the one that contains the leukemic cells themselves. The polymerase chain reaction was used to examine cytokine expression, and flow cytometry was used to purify the various subsets of peripheral blood mononuclear cells examined in these studies, as well as to examine IL-7 receptor expression. A proportion of the cells from the CLL patients express receptors that are capable of binding IL-7, whereas T cell-depleted normal cell preparations do not express receptors for IL-7 that are detectable with IL-7 fluorokines. The IL-7 receptor-bearing cells in CLL patients include a portion of leukemic cells and a fraction of the T cells, as well as some non-T, non-B cells. These findings suggest that IL-7 and IL-7 receptor expression in CLL may be relevant not only to growth regulation of the leukemic cells but to the immunological abnormalities that occur in the disease as well, possibly via the induction of inappropriate immune activity of IL-7 receptor-bearing cells.


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